Kura Oncology, Inc. (KURA) Q2 2019 Earnings Report, Transcript and Summary

Good day, ladies and gentlemen and welcome to the Q2 2019 Kura Oncology Earnings Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct the question-and-answer session, and instructions will follow at that time. [Operator Instructions]. As a reminder, this conference is being recorded. I would now like to introduce your host for today's conference Pete De Spain, Vice President of Investor Relations with Kura Oncology. You may begin.

Thank you, operator. Good afternoon and welcome to Kura Oncology's second quarter 2019 conference call. Joining me on the call from Kura are Dr. Troy Wilson, our President and Chief Executive Officer; and Dr. Marc Grasso, our Chief Financial Officer and Chief Business Officer; Dr. Antonio Gualberto, our Chief Medical Officer and Head of Development is also with us and available to answer questions. Before I turn the call over to Dr. Wilson, I would like to remind you today's call will include forward-looking statements based on current expectations. Such statements represent management's judgment as of today and may involve risks and uncertainties that could cause actual results to differ materially from expected results. Please refer to Kura's filings with the SEC, which are available from the SEC or on the Kura Oncology website for information concerning risk factors that could affect the company. With that, I'll now turn the call over to Dr. Troy Wilson, President and CEO of Kura Oncology.

Thank you, Pete, and thank you all for joining us this afternoon. The past quarter was highlighted by exciting data from our ongoing Phase 2 trial of tipifarnib in relapsed or refractory peripheral T-cell lymphoma. The data presented at both the European Hematology Association Annual Congress in Amsterdam and the International Congress on Malignant Lymphoma in Lugano marked the first prospective validation of CXCL12 pathway biomarkers to enrich for clinical activity of tipifarnib. The data showed a significant association between CXCL12 expression and clinical benefit including high levels of activity in both expansion cohorts: patients with angioimmunoblastic T-cell lymphoma an aggressive form of T-cell lymphoma often characterized by high levels of CXCL12 expression, and patients with PTCL who lack a single nucleotide variation in the 3-prime untranslated region of the CXCL12 gene. We believe these data are strong enough to support potential registration of tipifarnib in both patient populations and we intend to have discussions with regulatory authorities and key opinion leaders around next steps for the program. In addition, based on the extraordinary activity observed thus far, we plan to continue enrolling patients in the AITL cohort of our Phase 2 trial in order to acquire more experience regarding safety and tolerability in this population, and we expect to provide additional data from this cohort at a medical meeting later this year. We believe that based upon the revised 2017 WHO classification of T-cell lymphomas, AITL and related lymphomas represent approximately one-third of all PTCL cases. Our approach in CXCL12 driven PTCL has been consistent with the development strategy in HRAS mutant head and neck squamous cell carcinoma. We're primarily focused on indications where we can potentially drive single agent activity with durable objective responses. Further we seek to identify the subsets of patients who are most likely to respond to treatment. Such indications ideally can be pursued with smaller single arm registration-directed studies. Once we establish a foothold in a given indication, we can work toward broadening to earlier lines of therapy and expanding to larger patient populations either as a single agent or in combination approaches. In addition to establishing clear clinical proof of concept in T-cell lymphomas, we believe we've made significant progress toward broadening tipifarnib's potential to treat other CXCL12 driven indications of high unmet need. For example, we recently reported retrospective data from a Phase 2 trial of tipifarnib in patients with relapsed or refractory lymphomas. Our analysis identified pretreatment tumor CXCL12 expression and CXCL12 reference sequences as potential biomarkers of clinical benefit in patients with diffuse large B-cell lymphoma and mycosis fungoides, the most common form of cutaneous T-cell lymphoma. Further, recall earlier this year, we reported the identification of a potential association between CXCL12 expression and clinical benefit from tipifarnib in patients with pancreatic cancer. We continue to do additional pre-clinical work to validate tipifarnib in a CXCL12-high subpopulation of pancreatic cancer patients, and we expect to initiate a proof of concept study early next year. Over time, we believe CXCL12 pathway biomarkers could enable registrational strategies for tipifarnib in multiple hematologic and solid tumor indications. Now let's turn our attention to our most advanced program, HRAS mutant head and neck squamous cell carcinoma or HNSCC. The primary focus of the company continues to be the execution of our initial registration-directed trial of tipifarnib. To recap, the treatment cohort of our registration-directed study, which we call AIM-HN is to enroll -- which we call AIM-HN is designed to enroll at least 59 evaluable patients with HRAS mutant HNSCC, who have received prior platinum-based therapy. AIM-HN initiated in November 2018 and it is expected to take approximately two years to fully enroll. Meanwhile, we've enrolled additional patients in our ongoing Phase 2 trial of tipifarnib in HRAS mutant HNSCC, which we call RUN-HN. We plan to provide an update from RUN-HN at a medical meeting later this year. The update is expected to include follow up from ongoing patients as well as preliminary data on newly enrolled patients in both the HNSCC and other SCC cohorts. We remain enthusiastic about the potential for tipifarnib to treat patients with HRAS mutant tumors. Although our initial registration will focused on relapsed and/or refractory HRAS mutant HNSCC patients having HRAS variant allele frequency measurements greater than or equal to 20%, we see a broader opportunity set that includes combination therapies with immune therapies, cetuximab, and potentially chemotherapy. We intend to pursue these expanded indications as our resources permit. Consistent with our perspective on a larger set of development opportunities for tipifarnib, I'm pleased to report we've also expanded the patent protection for tipifarnib in both the U.S. and Europe. Last month we announced that the U.S. Patent and Trademark Office issued two new patents; a method of treating patients with HRAS mutant HNSCC with any farnesyl transferase inhibitor; and a method of treating patients with HRAS mutant non-small cell lung carcinoma with tipifarnib. In addition the European Patent Office granted a patent directed to the use of tipifarnib as a method of treating patients with HRAS mutant HNSCC. Each of these patents has an expiration date of August 2036 excluding any possibly patent term extension. These new patents strengthen our competitive advantage as we continue to advance the development of tipifarnib. We now own a number of independent issued patents covering tipifarnib and HRAS mutant HNSCC and we will continue to aggressively pursue additional intellectual property protection in the U.S. and abroad. Now, let's spend a moment on each of our emerging pipeline programs beginning with our ERK inhibitor KO-947. KO-947 is a potent and selective small molecule inhibitor of ERK which we are advancing as a potential treatment for patients with tumors that have dysregulated activity in the MAPK pathway. Our preclinical data suggest that KO-947 has anti-tumor activity in KRAS or BRAF mutant adenocarcinomas as well as certain subsets of squamous cell carcinomas. We continue to evaluate dosing regimens for KO-947 with a goal of reaching a recommended Phase 2 dose or maximum tolerated dose. We anticipate completing the dose escalation portion of our Phase 1 trial by the end of this year. In conducting the dose escalation trial for KO-947 our goals are to establish: a go-forward dosing schedule; an understanding of the safety and tolerability profile; pharmacokinetic and pharmacodynamics data; some ERK inhibition or other biomarker data; and any early signs of anti-tumor activity. Although most of the patients in the dose escalation portion of our study will be in difficult to treat populations such as pancreatic and colorectal cancer we believe our Phase one strategy will provide a solid foundation to make data-driven decisions for KO-947's best path forward. Our other emerging pipeline program is KO-539 a potent and selective small molecule inhibitor of the menin-mixed lineage leukemia or menin-MLL protein-protein interaction. We've generated preclinical data that support the potential anti-tumor activity of KO-539 in genetically defined subsets of acute leukemia including those with rearrangements or partial tandem duplications in the MLL gene as well as those with oncogenic driver mutations in genes such as NPM1. Last week we announced the FDA has granted Orphan Drug Designation to KO-539 for the treatment of acute myeloid leukemia. This decision by FDA follows the clearance of our investigational new drug application in March and it recognizes the potential for KO-539 to address a population of patients with high unmet need. Regulatory and clinical reviews have now been completed and we're in the final stages of study startup for our Phase 1 clinical trial of KO-539 in relapsed or refractory AML. With that I'll turn the call over to Marc Grasso for a discussion of our financial results for the second quarter of 2019.

Thank you, Troy and good afternoon everyone. I'll provide a brief overview of our financial results here on the call and invite you to review our 10-Q filed today for a more detailed discussion. Research and development expenses for the second quarter of 2019 were $11.4 million compared to $11.5 million for the second quarter of 2018. The slight decrease in R&D expenses for the quarter was primarily due to a decrease in clinical development activities related to our Phase 2 trial of tipifarnib, offset by an increase in clinical development activities related to our registration-directed trial for tipifarnib. General and administrative expenses for the second quarter of 2019 were $4.5 million compared to $3.8 million for the second quarter 2018. The increase in G&A expenses was primarily due to increases in personnel costs and non-cash share-based compensation. Net loss for the second quarter 2019 was $14.9 million or $0.38 per share compared to a net loss of $14.7 million or $0.45 per share for the second quarter 2018. As of June 30th, 2019, we had cash, cash equivalents, and short-term investments of $261.4 million compared with $179.0 million as of December 31st, 2018. This includes net proceeds of approximately $108 million from the public offering we completed in June 2019. By way of updated guidance post the offering, we expect that our current cash, cash equivalents, and short-term investments will be sufficient to fund current operations into the second half of 2021. We believe we remain in a strong position to execute on our ongoing registration-directed trial for tipifarnib in HRAS-mutant HNSCC. In addition, we have the opportunity to capitalize on our positive Phase 2 data in PTCL explore additional indications for tipifarnib accelerate pre-NDA efforts and advance the next-generation farnesyltransferase inhibitor program as well as devote additional resources toward our emerging pipeline programs. With that, I will now turn the call back over to Troy.

Thank you, Marc. We entered the latter half of this year in a strong position armed with two distinct clinically validated biomarkers for tipifarnib, two emerging pipeline programs and the financial resources to better realize the potential value of these assets. Before we jump into the Q&A session, let me quickly lay out our anticipated milestones for the remainder of this year and early next year. For tipifarnib, additional data from our Phase 2 trial in HRAS-mutant HNSCC and other HRAS-mutant SCCs in the fourth quarter of 2019; additional data from the AITL expansion cohort in our ongoing Phase 2 trial in the fourth quarter of 2019; additional data from our Phase 2 trial in chronic myelomonocytic leukemia in the first half of 2020; and initiation of a proof of concept study in pancreatic cancer in the first half of 2020. For KO-947, completion of the dose escalation portion of our Phase 1 trial by the end of 2019, and for KO-539 initiation of our Phase 1 trial in the second half of 2019. With that operator, we're now ready for questions.

[Operator Instructions] And our first question is from Konstantinos Aprilakis from Deutsche Bank. Your line is now open.

Good afternoon, guys. Thanks for taking my questions and congrats on all progress this quarter. So with regard to AIM-HN, I was wondering if you could provide some color on the proportion of patients who screened for enrollment that meet the relevant cut-offs that you've set for HRAS-mutant allele frequency in serum albumin.

Sure. Konstantinos, thanks for the question. Antonio, do you want to address Konstantin's question?

Yes, Konstantin. It's 5%. So the actual data actually confirmed the estimate that we did. So, one out of 20 patients.

[Indiscernible] world. Okay.

Yes, 5%, yes.

Oh, that's great. And then is the goal still to involve like 100 clinical centers enrolling patients and then how many of those sites are open, if that's the case?

Approximately that's the number. You know, we're obviously not releasing numbers on the percentage of sites that are open.

Okay. And then for just switching gears a bit to KO-539. So, I was wondering can you share sort of the some detail on that trial the size, the design and maybe the latest thoughts in biomarker selection strategy. Are you still planning to look at partial tandem duplication in MLL as well as NPM1 and DNMT3A driver mutations?

Antonio, you want to go ahead and take that?

Yeah. So this will be an AML relapsed/refractory population. In principle, the dose escalation is going to happen. Accelerated portion is not going to have initial selection of patients, but the intent is to once we are getting close to recommend Phase 2 dose they make the switch to the rearrangement the NPM1 mutant population in the enrolled patients.

Okay, great. Thanks, guys.

Thanks, Konstantin.

Thank you. Our next question is from Tyler Van Buren from Piper Jaffray. Your line is now open.

Hey, guys. Good afternoon. Thanks for taking the questions. I had a question on the ERK data update by year-end. You gave us some additional color there, and spoke about pancreatic and colorectal. But I guess -- and you seem pretty confident in having the dose ranging done by year end. But the trial, my understanding is that it's been going on for a while. So could you just discuss the time frame that you've been evaluating this program for the number of patients enrolled, and also a little bit more specificity around the challenges with respect to dosing and dosing regimen and whether you think it could drive monotherapy responses or is more likely to be a combination partner.

Sure, Tyler. Thanks for the question. I'll share my thoughts, and then invite Antonio to comment. The opportunity with KO-947 is that you're inhibiting ERK, which we know is the central actor in tumor cells. It's also a very important protein in normal cells. And consistent with other inhibitors of the MAP kinase pathway, including MEK inhibitors and even other ERK inhibitors, you know that along with clinical activity is going to come toxicities. And those toxicities are pretty well understood. They include rash and diarrhea and GI. Those are the pretty common toxicities. Our approach with KO-947, because we could see prolonged pathway inhibition with intermittent dosing and we could dose with IV formulation, we thought perhaps we could get to higher exposures in patients and in the tumors with intermittent IV dosing. So that's been the approach that we've taken. The team has been prosecuting a couple of different doses and schedules. And this is unfortunately something that can only really be done empirically. There isn't a computer program or anything that's going to allow you to model it. You give the patients as much drug as they can take and then you have to introduce a holiday and those holidays are empirically defined. So to draw an analogy to tipifarnib, we give tipifarnib 600 milligrams twice a day one week on and one week off. The one week off is the holiday needed to sustain that high dosing. We are working toward a dosing schedule for ERK that we think will put us in a position to pursue either an approach as a monotherapy or in combination. As long as we keep going, I think we continue to be encouraged. It is just something that one has to do slowly in Phase 1. If you see something you have to expand and then keep going and that's really where we are. We get the question frequently, are we looking in selected populations, which is why we're giving people the color that as would be expected in a Phase 1 unit, most of the patients are end-stage pancreatic or colorectal where there's really, particularly at lower sub-therapeutic doses you're just not expecting to see very much. We do have clear biomarker defined populations that we can go into both as a monotherapy and combination but we need a recommended Phase 2 dose and schedule to get there. And I think the team is making good progress. It's never over until it's over. We expect that it may take the rest of this year to finalize the Phase 1 and so that's why we're guiding that the earliest we could present the data would be early next year and we're trying to give some color on the data that people might expect. Let me pause there and just invite Antonio, if he wants to add anything to my comment.

Just to mention that, obviously, there have been multiple failure targeting this pathway. There have been some subsets in BRAF melanoma for example. But we know that the pathway is really about in pancreatic cancer and we have our data in the squamous tumors, and we know how to select those patients. So by using an IV, we can get higher exposures that you could ever get with an oral compounds, many of the oral compounds have issues of bioavailability and issues of GI tox. So we can get high exposures with the IV. And, of course, if you give a daily IV you're going to reach the fee applications very quickly. But that's really not feasible in the long-term, so you need to be working those regimens. Do I give an IV every three days or give it every seven days? When we see maculopapular rash, how many days do you have to use I'll say, holiday. So that's what Troy's referring to that all these things have to be done empirically, so you get the best possible recommended Phase 2 dose before you do the real testing in the massive population in a Phase 1 extension or in a Phase 2. We have done extensive work in animals in PDX models more than 250 PDX models so we know what are the potential more sensitive tumors. So we now need to get a good recommended Phase 2 dose to test the hypothesis. Q – Tyler Van Buren: Great. Thanks very much for the detail comments.

Pleasure.

Thank you, Tyler.

Thank you. Our next question is from Jonathan Chang from SVB Leerink. Your line is now open.

Hi, thanks for taking my questions, and congrats on the progress. First question, can you help set investor expectations ahead of the fourth quarter RUN-HN update? How much more data should investors expect versus the last update?

Antonio would you like to take Jonathan's question?

Certainly we will present every single patient that have been enrolled in the trial until the date of presentation. That will include every patient enrolled in the head and neck as well as any of the squamous patients. We need to provide a balance between enrolling in the pivotal and enrolling in the Phase 2. So, yes, we will have some patients but as you can imagine our focus is to enroll the pivotal study. We only enroll in the Phase 2 if a patient have identified in a site in, which the pivotal study is still not yet open. So I cannot give you a number of the percent. Again we will present every single patient enrolled. But you cannot expect very high numbers because we tried to accelerate the pivotal as much as we can.

Got it. Appreciate the color. Second question. How are you thinking about KO-947 from a potential clinical collaboration or partnership standpoint?

Yeah, Jonathan thanks for the question. I think it goes back to what we were saying earlier which is a critical question in anyone's mind looking at an agent whether as a monotherapy or in combination is what's the recommended Phase 2 dosing schedule? What are the signals that you're on target? And then of course, what are the associated toxicities? What's the tolerability profile? There is certainly interest both as a monotherapy. We obviously -- Antonio mentioned squamous head and neck. We have insight into that population through our expanding network of head and neck sites. So we're keenly interested in the 11q13 amplified population as you know from our preclinical data. But there's also interesting opportunities to combine with other agents on the MAP kinase pathway, the PI3 kinase pathway potentially agents that are critical to the cell cycle control and we'll be I think in a good position to determine the next steps forward. We keep all the options on the table as far as partnering is concerned across the pipeline.

Got it. Thanks for taking my question.

Sure. Thank you.

Thank you. Our next question is from Jay Olson from Oppenheimer. Your line is now open.

Hey, guys. Congrats on the progress and thanks for taking my questions. I wanted to start with the recently issued patents. Congratulations on those. I'm curious about the broad method of use patent for the entire class of farnesyltransferase inhibitors. Would that block the freedom to operate for other molecules that you don't own to be studied in that space?

So, Jay, thanks for the question. If you take a step back what the field of farnesyltransferase inhibition was missing was an identification of the biomarkers that would allow for rational selection strategies. Janssen had treated 5,000 patients across 70 different trials. Anecdotal reports of activity, but never enough activity to sort of drive a registrational program. It was the combination of the molecular and the clinical insights that we had an understanding of the biology and then a whole lot of both clinical and preclinical work that has gone into the disclosures that are supporting these patents. And as much as we can we've tried to kind of bring investors along and the market along with this because this is an unusual situation. You don't typically see a compound out there with such a demonstrated track record of clinical activity without an understanding of how it works. Probably the last example maybe was the IMiDs, right -- the IMiD franchise with Revlimid and pomalidomide and before that thalidomide. And so to your specific question the patent that issued from the U.S. Patent and Trademark Office the claim covers a method of treating patients with HRAS mutant head and neck squamous cell carcinoma using any farnesyltransferase inhibitor. So our read of that is yes, if there is an FTI even including a new molecule one that's just been invented that uses that biomarker method as a method of enrichment for patients then you would be covered by that patent claim. And you can imagine that we are taking this same strategy across each of our biomarker initiatives whether it's CXCL12 wherever it may be. And we'll have more to say about that in the months and years to come. But I think it's really -- we were very, very pleased that the patent office recognized sort of our pioneering position in the farnesyltransferase inhibitor space and in really providing the missing link that's allowed us to unlock the clinical and hopefully the commercial value.

Great. Thanks for that additional color. That's very helpful. And then I did want to maybe just follow-up on KO-947. Could you maybe outline your target product profile for that molecule and maybe map out the scope of the commercial potential?

Yes. So the target product profile Antonio spoke to it in his comments. At least at this stage we're expecting it's going to be an IV formulation. We are pursuing a weekly schedule. We're also pursuing an intermittent schedule that is more frequently than weekly. And then I think probably the next appropriate thing to talk about is the target population. And there we've done an extensive survey preclinically to try to identify those tumors with specific characteristics that are responsive to inhibition by 947 as a monotherapy. And we've shown that preclinical data. We've published it at AACR. It includes examples of BRAF and KRAS mutant adenocarcinoma. It also interestingly includes head and neck squamous and esophageal squamous cell carcinomas that have 11q13 amplifications. But that's preclinical. Obviously, there's work to be done clinically. And as Antonio mentioned, we're optimistic that we'll have an opportunity either as a Phase 1 extension or a Phase 2 trial to be able to evaluate 947 in some selected populations. We haven't said yet, what those are but obviously we have a keen interest in head and neck. In terms of the potential, our understanding and this is all preliminary data is the 11q13 amplification is 20% to 25% of head and neck. It's perhaps even larger in esophageal. So those are pretty significant populations. And of course, we're well acquainted with the high unmet need in the squamous cell – in the head and neck HNSCC population. So, the challenges of inhibiting ERK in terms of finding a dose and schedule and an acceptable tolerability are offset by the fact that it is – these are some very significant populations that we're talking about. And we hope by the end of this year, as we've said to be in a position where we've got a good working understanding of the drug and then we can really start to explore it in some more – some populations where we might expect to see some encouraging signs of clinical activity. Does that answer your question?

Yes. That's perfect. Thank you for taking the questions.

Sure.

Thank you. Our next question is from Joel Beatty from Citi. Your line is now open.

Hi. Thanks for taking the question. Could you provide an overview of the opportunity for tipifarnib in HRAS-positive squamous cell carcinoma beyond what's currently being focused on in the Phase 2 AIM-HN trial either other head and neck patients or tumors other than head and neck?

Yeah, thanks Joel for the question. So to the earlier question that Antonio answered, we think that when you define the population as HRAS mutant HNSCC patients with a tumor allele – a variant allele frequency greater than 20%, our best guess is that's about 5% of the head and neck population across all lines of therapy. We do think there's a significant population of head and neck patients who have HRAS mutant variant allele frequencies lower than 20%, and of course we're excluding those from the registrational study, because we don't see responses as a monotherapy. We do think there's an opportunity to treat those patients either sequentially or in combination with other agents and in my comments I called out potentially combinations with immune therapy with cetuximab potentially with chemotherapy. Those are not clinical studies that we have even planned yet, but certainly places for expansion. I think stepping even kind of one level higher – in our corporate presentation we've guided to there may be as many as 7,500 HRAS mutant patients in the squamous cell carcinomas generally. And that would include not just head and neck, but lung and other histologies as well. And we may – to reach those patients, it may not be a response rate driven trial. It may be a time to endpoint, or a survival trial. We're going to have to step our way through that. But I think what we're encouraged by is these HRAS mutant tumors are not responsive to our knowledge to any other therapy. They don't respond to immune therapy. They don't respond to cetuximab. They respond to varying degrees to tipifarnib. And then it becomes a matter of how you thoughtfully expand your label from our initial relapsed/refractory head and neck to potentially be able to move to those other populations. So hopefully, our corporate presentation gives you some guidance on the HRAS population. I think that's with the caveat that it's going to take monotherapy in the initial instances and then combination or sequential treatment as you look to broaden out the label.

Great. Thank you.

Sure.

Thank you. [Operator Instructions] And our next question is from Chris Shibutani from Cowen. Your line is now open.

Great. Thanks very much. One specific question on the ERK inhibitor and then maybe a bigger picture broader one. On the ERK inhibitor, Troy based upon what you guys know so far when you contemplate potential combinations can you describe any particular agents that you think would be logical candidates for a combination work?

Yes, Chris. Thank you for the question. I mean, I want to be a little bit guarded here both from a development and an intellectual property perspective. I've kind of alluded to this in that there would be a logical rationale to combine with other inhibitors of the MAP kinase pathway. Combinations with inhibitors of the PI3 kinase pathway might also make sense and then certain instances of cell cycle agents that are disrupting the cell cycle. I think, we're going to be driven by what we see as a monotherapy. Whether you're going forward as -- and in combination you want to ensure that you've got a good understanding and the robust amount -- a robust level of monotherapy activity. That can be either responses or it can be disease stabilization but I think we want to understand that. But let me invite Antonio to comment if he wants to add anything. I'm just kind of giving you general comments until we get sort of toward the end of the year and into next year and have more clarity.

So Troy, I would only add that it's very attractive to consider the combination with other molecularly targeted therapies. But you also have to think in development you have to consider the bread and butter of combining with a standard of care. So if you have activity in head and neck in a subset you're probably going to do the combinations with cetuximab with cisplatin with pembrolizumab in order to expand your label horizontally. Similar to your comment before about tipifarnib yes, we can expand horizontally, but it's the right particular subset in which you have very high activity you can move vertically treating in your adjuvant setting. That's the basis for adjuvant treatment. Adjuvant treatment it could be one or two years of treatment. So it's a large opportunity once you identify the subset that is very sensitive to proceed vertically to larger populations and also as you indicated horizontally. We target it separately, but obviously with the standard of care. And then you are being carried by the therapy. You are being carried by the cetuximab chemotherapy combinations, but for both cases for tipifarnib and for 947.

Great. And then a question about tipifarnib the lead asset which you guys have been working diligently on for a while now. Is it reasonable to believe that your experience is changing as you continue to pursue the clinical development? By that I'm trying to gauge, is it getting easier to find the patients and as you're continuing to enroll patients is there some sort of transition that's occurring in terms of the type of patients that are coming forth. So that as we think about the experience with the Phase three enrollment should we think about the mix of patient backgrounds somehow altering or shifting or perhaps even improving that would maybe impact either the timing of completion or the probability of success of the outcome?

Yes, Chris. I might answer the question the following way. First of all, nothing is easy. And it's a great credit to Antonio and the entire team for what they've been able to do to move tipifarnib to where it is today. One of the biggest challenges with any registrational trial is just the scope and complexity of up to 100 sites worldwide however many different languages. This is not a continuation of the Phase 2. This is an entirely new study. And it's the little things that you have to pay attention to. It's the contracts the IRB reviews. We are screening 1,500 patients to be able to find the 74 that will allow us to conduct AIM. And the team is making great progress in executing on the study. I wouldn't say it's easier. I would say they understand the task. And fortunately, we've got a lot of experienced people who have done registrational trials. And understand what you need to do to execute at this scale on a global basis. But again let me invite Antonio, if he wants to add anything to my comments.

So Troy, I will just mention that. Obviously the discovery of the biomarker interaction with CXCL12, opening an opportunity that is much larger than what we saw initially with HRAS in lymphomas, in myeloma, in solid tumors. Think about the potential CXCL12 target population. In pancreatic cancer it's one-third of pancreatic cancer. So obviously sign of the discoveries because it can be translated from one tumor to another or at least those tumors in which CXCL12 is a negative prognostic makes things in a way easier because we are reproducing interactions that we have confirmed previously. Then there's another aspect of this the technical aspect. So currently, we have NGS panels that determine the target for tipifarnib and the targets KO-947. So we mentioned before the 11q13 amplification. So those genes that determine what patient population they are -- is susceptible to 947 we can already see, when we do the screening for tipifarnib, because it's the same platform. So the more experience that we acquire with these tools. The better the relationship we have with the clinical sites. Then we can move compounds in indications, in settings, in clinical sites which we have already a good relationship. So, in a way, it's always difficult. But certainly experiences it will help with the development of subsequent drugs.

Great. Thank you for the comments. And it's great to see the portfolio and the pipeline continue to broaden. I think it's very positive. Thanks very much.

Thank you, Chris. And thanks again for participating in our call today. We'll be at the Wedbush Healthcare Conference in New York in a couple of weeks. Look forward to seeing a number of you there. In the meantime, if you have any additional questions, please feel free to contact Pete, Marc or myself. Thanks again. And have a good evening, everyone.

Ladies and gentlemen, thank you for your participation in today's conference. This concludes the program. You may now disconnect.